Chronic mild stress induces widespread decreases in thyroid hormone alpha1 receptor mRNA levels in brain--reversal by imipramine.
While considerable clinical evidence implicates thyroid hormones (THs) in depressive illness, the specific nature of this involvement remains unclear. The alpha1 subtype (TR-alpha1) is the most abundant TH receptor in brain. Here we investigated changes in TR-alpha1 mRNA in the chronic mild stress (CMS) model of depression. Rats were exposed to a CMS schedule for 3 weeks, which resulted in a progressive decreases in sucrose preference (an index of anhedonia). They were then treated daily with either imipramine (IMI, 10mg/kg) or vehicle (VEH) for 2 weeks before being sacrificed for quantitative in situ hybridization analyses of TR-alpha1 mRNA throughout the brain. Results indicated that CMS followed by VEH induced widespread decreases in TR-alpha1 mRNA in brain. In contrast, CMS-exposed rats receiving IMI for the last 2 weeks prior to sacrifice showed full recovery of sucrose preference. Furthermore, brain TR-alpha1 mRNA levels in these animals were similar to those of non-stressed controls receiving either SAL or IMI. These results reveal that TR-alpha1 mRNA brain levels are very sensitive to CMS effects. The reversal of both anhedonic and TR-alpha1 effects of CMS by IMI suggests that TR-alpha1 may play a role both in stress-induced depressive symptoms and in their reversal by antidepressant interventions.
Stein
Edward J
EJ
Neuroimaging Research Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ont., M5T 1R8 Canada; Pharmacology Department, University of Toronto, Toronto, Ont., Canada.
Filho
Nylson G da Silveira
NGDS
Biopsychology Department, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
Machado
Danilo C
DC
Biopsychology Department, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
Hipólide
Débora C
DC
Biopsychology Department, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
Barlow
Karen
K
Neuroimaging Research Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ont., M5T 1R8 Canada.
Nobrega
José N
JN
Neuroimaging Research Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ont., M5T 1R8 Canada; Pharmacology Department, University of Toronto, Toronto, Ont., Canada. Electronic address: jose_Nobrega@camh.net.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological; D013315:Stress, Psychological; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism*
D000928:Antidepressive Agents; D012333:RNA, Messenger; D037021:Thyroid Hormone Receptors alpha; D007099:Imipramine